The program of interdisciplinary research proposed in this investigation will employ correlative scanning-transmission electron microscopy (STEM) coupled with immunoautoradiography and microangiography to assess the cellular interaction and fine structural correlates of neural induction mechanisms that may transpire between normal peptide producing fetal hypothalamic grafts placed into the third cerebral ventricle of adult Brattleboro rats with autosomal homozygous diabetes insipidus. In host animals that exhibit a return to normal physiological parameters of urine osmolarity and drinking behavior, brains will be examined to determine the patterns of neuronal integration between normal vasopressin producing neurons of the fetal transplant and the surrounding host hypothalamus that is incapable of producing this peptide. This program of reseach will confront such fundamental issues as: 1) What are the major routes of delivery of centrally acting peptides? 2) What are the fine structural correlates of synaptogenisis and neuronal plasticity between elements of the host brain and neural transplants? 3) What are the inductive effects of a neuropeptide producing transplant upon a host brain denied this capacity due to congenital neuropathy? 4) What are the underlying mechanisms of formation of the vascular patterns and neurovascular interrelationships that develop and originate from the host brain to maintain a viable neuropeptide-producing transplant? This experimental regimen has very clear health related potentials as a forerunner to neurosurgical replacement or substitution therapy in humans.